Abstract LB-326: Synergistic therapeutic effects of cytokine-induced killer (CIK) cell and temozolomide against glioblastoma

Abstract

The presence of active immunity within the brain supports the possibility of effective immunotherapy for glioblastoma (GBM). To provide a clinically-relevant adoptive immunotherapy for GBM using ex vivo expanded cytokine-induced killer (CIK) cells, the treatment capability of CIK cells, either alone or in combination with temozolomide (TMZ) were evaluated. Human CIK (hCIK) cells were cultured from PBMC using activating anti-CD3 antibody and IL-2, which were 99% CD3+, 91% CD3+CD8+ and 29% CD3+CD56+. In vitro, hCIK cells showed tumor-specific cytotoxicity against U-87MG human GBM cells. When hCIK cells were injected into tail veins of immune-compromised mice bearing U-87MG tumors in their brains, numerous CIK cells infiltrated into the brain tumors. CIK treatments (1 × 105, 1 × 106 or 1 × 107, once a week for four weeks) inhibited the tumor growth significantly in a dose-dependent manner; 44%, 54% and 72% tumor volume reduction, respectively, compared with the control group (P < 0.05). Moreover, hCIK cells (1 × 107, once a week for four weeks) and TMZ (2.5 mg/kg, daily for 5 days) combination treatment further increased tumor cell apoptosis and decreased tumor cell proliferation and vessel density (P < 0.05), creating a more potent therapeutic effect (95% reduction in tumor volume) compared with either hCIK cells or TMZ single therapy (72% for both, P < 0.05). Taken together, CIK cell-immunotherapy and TMZ chemotherapy have synergistic therapeutic effects and could be combined for a successful treatment of GBM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-326.

NKG2D- and T-cell receptor-dependent lysis of malignant glioma cell lines by human γδ T cells: Modulation by temozolomide and A disintegrin and metalloproteases 10 and 17 inhibitors

“… 27,51 However, combination treatment with TMZ and adoptively transferred human cytokin-induced killer cells showed synergistic therapeutic efficacy in a xenograft mouse model with transplanted U-87MG cells. 52 Such a synergistic therapeutic effect might be also envisaged with γδ T cells.…”

Temozolomide increases MHC‐I expression via NF‐κB signaling in glioma stem cells

“…Recent studies have shown that immunotherapy with TMZ is feasible for glioma treatment (Kim et al, 2007;Jin et al, 2011). Recent preclinical studies have shown that vaccination with dendritic cells followed by chemotherapy increases glioma patient survival (Liu et al, 2006).…”

The PD-1/B7-H1 Pathway Modulates the Natural Killer Cells versus Mouse Glioma Stem Cells

“…Adoptive immunotherapy is dedicated to taking advantage of cytokine-induced killer cells (CIK cells) and lymphokine-activated killer cells (LAK cells) to treat GBM. For CIK cells, human PBMCs are traditionally required to be incubated for 4 weeks with numerous cytokines to generate CIK cells [ 43 ]. Moreover, LAK cells, as immunotherapeutic agents, also have some disadvantages, such as a short in vivo lifespan, poor cytotoxicity, and numerous side effects [ 44 – 45 ].…”

“…Tumor growth was determined with an animal magnetic resonance imaging (MRI) system (PharmaScan 7T, Bruker, Germany) on days 7, 14, 21 and 28. When the first MRI scanning confirmed the tumor formation on the 7th day after the tumor cells implantation, the PD-1 inhibited and non-inhibihted IL-2-stimulated NK cells (5×10 6 , in 100μl PBS) and PBS (negative control) were intravenously injected into the mice containing GL261GSCs tumors once a week for four weeks [ 29 ]. The tumor volume was calculated by measuring the MRI of the largest tumor portion and applying the following formula: (width) 2 x length x 0.5.…”